Fertility-sparing surgery and survival among reproductive-age women with epithelial ovarian cancer in 2 cancer registries.

BACKGROUND: This study examined predictors of fertility-sparing surgery (FSS) among reproductive-age women diagnosed with epithelial ovarian cancer (EOC). In addition, relationships between FSS and survival were assessed in models stratified by tumor characteristics. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program and the National Cancer Database (NCDB) were queried for women 44 years old or younger with a primary EOC. FSS included unilateral salpingo-oophorectomy and uterine preservation, whereas surgeries including bilateral salpingo-oophorectomy and hysterectomy were categorized as non-FSS. Logistic regression was used to estimate multivariable-adjusted odds ratios and 95% confidence intervals (CIs) for associations between clinical characteristics (eg, age at diagnosis and race) and FSS odds. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for FSS and overall survival in subgroups defined by stage and grade or by stage and histology. Analyses were stratified by database (SEER vs NCDB). RESULTS: This analysis included 9017 women (SEER, n = 3932; NCDB, n = 5085) with EOC diagnosed between the ages of 15 and 44 years. In both cohorts, factors associated with significantly higher FSS odds included a younger age, a more recent ovarian cancer diagnosis, and no adjuvant chemotherapy. FSS was significantly associated with lower overall survival among women with stage II to IV, serous EOC (SEER HR, 1.61; 95% CI, 1.22-2.12). Significant associations between FSS and survival were not observed in other subgroups defined by stage and grade or by stage and histology. CONCLUSIONS: FSS appears to be safe for certain women with EOC but was related to poor survival among women with advanced-stage, serous EOC. Confirmatory studies with information on fertility intentions are needed.

The prognostic significance of aortic lymph node metastasis in endometrial cancer: Potential implications for selective aortic lymph node assessment.

OBJECTIVES: To evaluate the prognostic impact of aortic vs. pelvic lymph node (LN) metastasis among women with endometrial cancer (EC). METHODS: Using data from the SEER 18 Registries we identified 3650 women with LN positive (stage IIIC) EC. We used Kaplan-Meier curves and log-rank tests to compare mortality between women with stage IIIC1 and IIIC2 disease. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between stage III sub-stage (IIIC1 vs. IIIC2) and survival. RESULTS: Endometrioid tumors were more common among women with stage IIIC1 than IIIC2 tumors (62.5% vs. 54.3%) while, non-endometrioid histologies were more common among stage IIIC2. In the multivariable model, stage IIIC2 was associated with higher all-cause (HR = 1.44, 95% CI = 1.22-1.69) and EC-specific mortality (HR = 1.49, 95% CI = 1.25-1.77) compared with IIIC1. Women with non-endometrioid EC had poor survival, in particular, women with carcinosarcomas had higher EC-specific mortality compared to women with endometrioid EC (HR = 3.32, 95% CI = 2.71-4.07). When stratifying women according to substage, older age and non-endometrioid histology were associated with higher EC-specific mortality. Compared to women with a pelvic-only LN dissection, women with pelvic and aortic dissections had lower all-cause (HR = 0.74, 95% CI = 0.63-0.88) and EC-specific (HR = 0.79, 95% CI = 0.66-0.95) mortality. CONCLUSION: Women with aortic LN positive EC are more likely to die from their disease. Older women and non-endometrioid histologies are more likely to have aortic LN involvement. Compared to women with a pelvic-only LN dissection, women with pelvic and aortic dissections had lower EC mortality.

High-Effort Coping and Cardiovascular Disease among Women: A Systematic Review of the John Henryism Hypothesis.

African-American women living in the United States experience higher cardiovascular disease risk (CVD) mortality compared to White women. Unique mechanisms, including prolonged high-effort coping in the face of discriminatory stressors might contribute to these racial disparities. The John Henryism hypothesis is a conceptual framework used to explain poor health outcomes observed among individuals with low resources who repeatedly utilize active coping to overcome barriers. The aims of our study were to summarize the literature related to John Henryism and CVD-related factors with a particular focus on women and to identify gaps for areas of future inquiry. We searched MEDLINE, EMBASE, Scopus, and CINAHL to identify literature that used the John Henryism Active Coping scale. Reviewers independently reviewed eligible full-text study articles and conducted data extraction. We qualitatively summarized the literature related to John Henryism and cardiovascular disease (CVD)-related health behaviors (e.g., smoking or physical activity) and risk factors (e.g., hypertension) with a focus on study populations inclusive of women. Our review included 21 studies that used the John Henryism Active Coping scale, of which 10 explicitly reported on the interaction between John Henryism and socioeconomic status (SES) and CVD-related factors. With respect to the original hypothesis, three studies reported results in line with the hypothesis, four were null, and three reported findings in opposition to the hypothesis. The remaining studies included in the review examined the main effects of John Henryism, with similarly mixed results. The literature related to the interaction between John Henryism and SES on CVD-related factors among women is mixed. Additional studies of John Henryism that incorporate biological measures, varied indicators of resources, and larger study populations may illuminate the relationship between coping and deleterious health outcomes among women.

The association between histological subtype of a first primary endometrial cancer and second cancer risk.

OBJECTIVE: To evaluate the risk of a second primary cancer after endometrial cancer according to histological subtype. METHODS: Using data from the 13 National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries we identified women diagnosed with a primary endometrial cancer between 1992 and 2014. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for second primary cancer risk (all anatomical sites combined and for individual anatomical sites) among patients with endometrial cancer compared with the general population, in the overall study population and according to histological subtype. RESULTS: Among 96 256 women diagnosed with endometrial cancer, 8.4% (n=8083) developed a second primary cancer. The risk of second primary cancer was higher among patients with endometrial cancer than in the general population (SIR=1.05, 95% CI 1.03 to 1.07). We observed significantly higher second primary cancer risk among women with high grade endometrioid (SIR=1.12, 95% CI 1.05 to 1.19), serous (SIR=1.24, 95% CI 1.11 to 1.38), carcinosarcoma (SIR=1.18, 95% CI 1.02 to 1.35), mixed epithelial (SIR=1.22, 95% CI 1.06 to 1.40), and sarcoma (SIR=1.28, 95% CI 1.12 to 1.45) compared with the general population, but not for women with low grade endometrioid (SIR=1.01, 95% CI 0.98 to 1.03) or clear cell (SIR=1.09, 95% CI 0.88 to 1.33) endometrial cancer. Women with low grade endometrioid endometrial cancer had significantly lower second primary cancer risks in the gum and other mouth (SIR=0.57, 95% CI 0.30 to 0.97), lung and bronchus (SIR=0.72, 95% CI 0.66 to 0.77), and lymphocytic leukemia (SIR=0.71, 95% CI 0.54 to 0.93) while women with high risk endometrial cancer histological subtypes experienced significantly higher second primary cancer risk at several anatomical sites. CONCLUSIONS: Risk of developing second primary cancersat all anatomic sites combined and at individual anatomical sites varied according to histological subtype. Clinicians should be aware that women with different histological subtypes carry different second primary cancer risks .

Intentional weight loss, weight cycling, and endometrial cancer risk: a systematic review and meta-analysis.

PURPOSE: Weight cycling, defined as intentional weight loss followed by unintentional weight regain, may attenuate the benefit of intentional weight loss on endometrial cancer risk. We summarized the literature on intentional weight loss, weight cycling after intentional weight loss, bariatric surgery, and endometrial cancer risk. METHODS: A systematic search was conducted using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases published between January 2000 and November 2018. We followed Preferred Reporting Items of Systematic Reviews and Meta-analysis (PRISMA) guidelines. We qualitatively summarized studies related to intentional weight loss and weight cycling due to the inconsistent definition, and quantitatively summarized studies when bariatric surgery was the mechanism of intentional weight loss. RESULTS: A total of 127 full-text articles were reviewed, and 13 were included (bariatric surgery n=7, self-reported intentional weight loss n=2, self-reported weight cycling n=4). Qualitative synthesis suggested that, compared with stable weight, self-reported intentional weight loss was associated with lower endometrial cancer risk (RR range 0.61-0.96), whereas self-reported weight cycling was associated with higher endometrial cancer risk (OR range 1.07-2.33). The meta-analysis yielded a 59% lower risk of endometrial cancer following bariatric surgery (OR 0.41, 95% CI 0.22 to 0.74). CONCLUSIONS: Our findings support the notion that intentional weight loss and maintenance of a stable, healthy weight can lower endometrial cancer risk. Strategies to improve awareness and maintenance of weight loss among women with obesity are needed to reduce endometrial cancer risk.

Detection of endometrial cancer cells in the fallopian tube lumen is associated with adverse prognostic factors and reduced survival.

OBJECTIVE: Stage is a critical determinant of prognosis and treatment for endometrial cancer (EC) patients. Women who have had a tubal ligation for sterilization have improved EC survival, secondary to lower stage at presentation, suggesting that transtubal spread may represent an important route of metastasis. We evaluated detection of intraluminal tumor cells (ILTCs) in relation to tumor characteristics and survival. METHODS: One pathologist retrospectively evaluated hematoxylin and eosin sections of routinely collected fallopian tubes for ILTCs from 295 EC patients, masked to outcome. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between demographic (age, race) and clinical [FIGO 2009 stage, lymphovascular space invasion (LVSI), histological subtype] characteristics and ILTCs. Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations between ILTCs and recurrence-free survival (RFS) and EC-specific survival, overall and stratified by histological subtype or stage. RESULTS: In univariable logistic regression models, age (55-64 vs. ≥65: OR = 3.41, 95% CI = 1.48-7.84), stage (stage IV vs. stage I OR = 14.58, 95% CI = 5.27-40.35), LVSI (OR = 2.93, 95% CI = 1.42-6.04), and histological subtype (serous vs. low-grade endometrioid OR = 3.21, 95% CI = 1.08-9.58), were associated with ILTCs. Only age and stage remained significantly associated with ILTCs in adjusted models. ILTCs were significantly associated with lower EC-specific survival among women with serous EC or stage I disease; however, adjustment for age, stage, and histology attenuated these associations. CONCLUSION: Our findings suggest that ILTCs are associated with adverse EC prognostic features and reduced survival in cases of early stage or serous histology.

Programmed Death Ligand 1 Expression Among 700 Consecutive Endometrial Cancers: Strong Association With Mismatch Repair Protein Deficiency.

OBJECTIVE: This study aims to determine the prevalence of programmed death ligand 1 (PD-L1) expression in endometrial carcinoma (EC) and determine clinical and pathological associations. METHODS: Immunohistochemistry for PD-L1 was performed on sections of a triple-core tissue microarray of 700 ECs. Positive PD-L1 expression, defined as 1% of cells staining positive, was evaluated in tumor and stromal compartments. Using age-adjusted logistic regression, we estimated odds ratios and 95% confidence intervals for associations between PD-L1 expression (overall and by staining compartment) with clinical and tumor characteristics. Kaplan-Meier plots and log-rank tests were used to evaluate associations between PD-L1 expression and EC-specific survival. RESULTS: PD-L1 expression was observed in 100 cases (14.3%), including 27 (3.9%) with expression in tumor cells only, 35 (5.0%) with expression in both tumor cells and stroma, and 38 (5.4%) with expression in stroma only. Expression was observed in ECs of different histologic types. Tumors characterized by loss of mismatch repair proteins were significantly associated with tumoral PD-L1 expression (P < 0.0001), but not with stromal PD-L1 expression. Both tumoral and stromal PD-L1 expressions were associated with high-grade endometrioid histology, nonendometrioid histology, and lymphovascular space invasion. We observed no significant associations between PD-L1 expression and EC-specific survival. CONCLUSIONS: PD-L1 is expressed in a significant proportion of EC and is associated with mismatch repair deficiency, potentially representing a mechanism of tumor immune evasion and a therapeutic target in EC.